Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism
Journal
Parkinsonism and Related Disorders
Journal Volume
15
Journal Issue
6
Pages
466-467
Date Issued
2009
Author(s)
Ross O.A.
Spanaki C.
Griffith A.
Kachergus J.
Haugarvoll K.
Latsoudis H.
Plaitakis A.
Ferreira J.J.
Sampaio C.
Bonifati V.
Zabetian C.P.
Farrer M.J.
Abstract
The Roc domain of the Lrrk2 protein harbors two pathogenic mutations which cause autosomal dominant parkinsonism (R1441C and R1441G). A third putatively pathogenic variant (R1441H) has been identified in four probands of diverse ethnicity with parkinsonism. Herein we show that the R1441H substitutions lie on different haplotypes within our patients, confirming this codon as a mutational hotspot. The absence of this variant in control subjects and the presence of two other pathogenic variants at this amino acid position collectively support the contention that R1441H is a pathogenic substitution. ? 2008 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
leucine rich repeat kinase 2; adult; amino acid substitution; article; autosomal dominant disorder; codon; ethnicity; gene mutation; haplotype; heterozygote; human; parkinsonism; priority journal; protein domain; Adult; Arginine; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Histidine; Humans; Male; Middle Aged; Parkinsonian Disorders; Polymorphism, Single Nucleotide; Protein-Serine-Threonine Kinases
Type
journal article